Case Report: Primary Hypothyroidism Associated With Lutetium 177-DOTATATE Therapy for Metastatic Paraganglioma

Front Endocrinol (Lausanne). 2021 Jan 21:11:587065. doi: 10.3389/fendo.2020.587065. eCollection 2020.

Abstract

Background: Lutetium 177 (177Lu) - DOTATATE is a form of peptide receptor radionuclide therapy (PRRT) utilized in the treatment of neuroendocrine tumors. Data on 177Lu-DOTATATE-induced thyroid dysfunction is limited.

Case description: A 29-year-old male with SDHB positive metastatic paraganglioma enrolled under the 177Lu-DOTATATE trial (NCT03206060) underwent thyroid function test (TFT) evaluation comprised of thyroid stimulating hormone (TSH) and free thyroxine (FT4) immunoassay measurements per protocol prior to 177Lu-DOTATATE therapy. The TSH was suppressed [<0.01 µIU/ml (0.27-4.2 µIU/ml)], and FT4 was normal [1.3 ng/dl (0.9-1.7 ng/dl)]. The TSH receptor antibody and thyroid stimulating immunoglobulin index were undetectable [<1 IU/L (≤1.75 IU/L), and <1 (≤1.3) respectively], while the anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies were elevated [605 IU/ml (0.0-34.9 IU/ml), and 178 IU/ml (0.0-40.0 IU/ml) respectively]. Mass spectrometry on a stored (-80°C) plasma sample obtained one-month pre-PRRT revealed elevated total triiodothyronine (TT3) [235 ng/dl (65-193 ng/dl)] and FT4 [3.9 ng/dl (1.2-2.9 ng/dl)] levels. The patient was diagnosed with Hashimoto's thyrotoxicosis. However, the patient was asymptomatic. One month after the first dose of 200mCi 177Lu-DOTATATE, the patient noted fatigue and a 2.6 Kg weight gain. The TSH (73.04 µIU/ml), anti-TPO antibodies (>1,000 IU/ml), and anti-Tg antibodies (668 IU/ml) had substantially increased, with reductions in FT4 (0.3 ng/dl) and TT3 [54 ng/dl (87-169 ng/dl)]. Diagnostic gallium 68 - DOTATATE positron emission tomography-computed tomography performed prior to 177Lu-DOTATATE treatment revealed diffuse thyroid uptake. Post-therapy single-photon emission computed tomography also revealed diffuse uptake of 177Lu-DOTATATE in the thyroid gland. Levothyroxine therapy was initiated, and the patient's symptoms resolved.

Summary: We report, for the first time, a patient with asymptomatic primary hyperthyroidism who rapidly developed symptomatic primary hypothyroidism 1 month after 177Lu-DOTATATE therapy, accompanied by marked changes in TFTs and thyroid auto-antibody titers, with functional imaging evidence of diffuse uptake of 177Lu-DOTATATE in the thyroid gland.

Conclusions: Thyroid dysfunction can be associated with PRRT. Thyroid uptake patterns on pre-treatment diagnostic somatostatin analog scans might predict individual susceptibility to PRRT-associated TFT disruption. Therefore, periodic evaluation of TFTs should be considered in patients receiving PRRT.

Keywords: DOTATATE; Lutathera; hypothyroidism; paraganglioma; peptide receptor radionuclide therapy.

Publication types

  • Case Reports
  • Clinical Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Asymptomatic Diseases
  • Hashimoto Disease / complications
  • Hashimoto Disease / diagnosis
  • Humans
  • Hypothyroidism / chemically induced*
  • Hypothyroidism / diagnostic imaging
  • Hypothyroidism / drug therapy
  • Male
  • Neoplasm Metastasis / radiotherapy
  • Octreotide / adverse effects
  • Octreotide / analogs & derivatives*
  • Octreotide / metabolism
  • Organometallic Compounds / adverse effects*
  • Organometallic Compounds / metabolism
  • Paraganglioma / complications
  • Paraganglioma / metabolism
  • Paraganglioma / pathology
  • Paraganglioma / radiotherapy*
  • Positron Emission Tomography Computed Tomography / methods
  • Radiopharmaceuticals / adverse effects*
  • Radiopharmaceuticals / metabolism
  • Succinate Dehydrogenase / metabolism
  • Thyroid Gland / diagnostic imaging
  • Thyroid Gland / metabolism
  • Thyroid Gland / pathology
  • Thyroxine / therapeutic use
  • Treatment Outcome

Substances

  • Organometallic Compounds
  • Radiopharmaceuticals
  • gallium Ga 68 dotatate
  • lutetium Lu 177 dotatate
  • SDHB protein, human
  • Succinate Dehydrogenase
  • Thyroxine
  • Octreotide

Associated data

  • ClinicalTrials.gov/NCT03206060